Varlilumab is an investigational therapy being developed by Celldex for the treatment of cancer.

How varlilumab works

Varlilumab is a human monoclonal antibody that targets the CD27 receptor protein produced by immune cells such as T-cells, B-cells, and NK-cells, and that is critical for their activation and proliferation. CD27 is also known to be overproduced by certain tumors such as B- and T-cell lymphomas.

Varlilumab may function through two independent mechanisms: by triggering the immune activation of lymphocytes or by providing direct therapeutic effects against tumors producing CD27.

Upon administration, varlilumab can bind to CD27 receptors, causing an increase in the proliferation and activation of T-cells and resulting in a long-lasting immune response.

Varlilumab can also bind directly to B-cell or T-cell-derived malignancies that produce CD27 at high levels, triggering their destruction through a mechanism known as antibody-dependent cellular cytotoxicity (ADCC). This may also lead to the halt of CD27-producing tumor cells.

Varlilumab in clinical trials

The safety and activity of escalating doses of varlilumab in 90 patients with solid tumors and B-cell and T-cell tumors producing CD27 are being evaluated in a Phase 1, open-label dose-escalation clinical trial (NCT01460134) in the U.S.

The results so far show evidence of biologic activity consistent with the CD27 stimulation of T-cells by varlilumab. One patient with metastatic kidney cancer experienced a 78 percent shrinkage of the tumor, and eight patients experienced stable disease for more than three months. No adverse events resulting from immune responses were observed.

A combination of varlilumab and Opdivo (nivolumab) is also being evaluated in a Phase 1/2 dose escalation and cohort expansion study (NCT02335918) in patients with drug-resistant advanced solid tumors.

The primary goals of the Phase 1 part of the study are to determine the safety, tolerability, and clinical benefit of the combination therapy and identify the best doses of varlilumab to be used in the Phase 2 part, the aim of which is to evaluate the clinical activity of the selected varlilumab dose(s) in combination with a flat dose of 240 mg of Opdivo in tumor-specific cohorts.

Preliminary results from the Phase 1 part in 36 patients showed the therapy was well tolerated without any evidence of increased autoimmunity or inappropriate immune activation. In addition, the investigators observed stable disease or better for at least three months in 80 percent of colorectal and ovarian cancer patients, and three partial responses leading to a shrinkage in the target tumors of between 49 percent and 95 percent.

The study, which is taking place in the U.S., is recruiting patients for its Phase 2 portion until early 2018. It is hoped that an estimated 205 patients will be enrolled.

Other details

The most common adverse effects associated with the use of varlilumab include fatigue, rash, nausea, headache, and diarrhea.


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